Celecoxib in Treating Patients With Early-Stage Rectal Cancer

Not Applicable

Terminated

• Conditions: Colorectal Cancer
• Interventions: Drug: celecoxib; Genetic: gene expression analysis; Genetic: protein expression analysis; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis; Other: mass spectrometry; Procedure: biopsy; Procedure: neoadjuvant therapy; Procedure: therapeutic conventional surgery

• Registration Number: NCT00608595
• Lead Sponsor: Vanderbilt-Ingram Cancer Center

Brief Summary

RATIONALE: Studying samples of tissue, blood, and urine from patients with cancer in the laboratory may help doctors learn more about changes that may occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how rectal cancer will respond to treatment with celecoxib.

PURPOSE: This clinical trial is studying how well celecoxib works in treating patients with early-stage rectal cancer.

Detailed Description

OBJECTIVES:

* Determine cyclooxygenase-2 (COX-2) over-expression in tumor specimens from patients with early-stage rectal cancer.

* Determine whether administration of a COX-2 inhibitor, celecoxib, results in changes in tumor (COX-2 overexpressing) levels of eicosanoids but not in levels in the surrounding normal tissue that is expected not to express COX-2.

* Determine whether surrogate markers of eicosanoid metabolism (i.e., serum VEGF levels, tumor prostaglandin E_2 \[PGE_2\], and the major urinary metabolite of PGE_2 \[PGE-M\]) in biological specimens from these patients correlate with changes noted in tumor tissue.

* Determine if there is a greater change in protein and gene expression from pretreatment biopsy levels in patient tumor specimens (COX-2 overexpressing) vs specimens of surrounding normal tissue (expected not to be COX-2 overexpressing).

OUTLINE: Patients receive oral celecoxib twice daily on days 1-5. Patients then undergo planned local excision or definitive radical resection on day 6.

Tumor tissue and normal tissue (at least 5 cm away from the tumor) samples are collected pretreatment. Post-treatment tissue samples are collected along with the surgery. Serum and urine samples are obtained at baseline and after administration of celecoxib. Tumor and normal tissue specimens are analyzed by assays measuring markers of cyclooxygenase-2 (COX-2) activity (i.e., COX-2 mRNA and protein, tumor prostaglandin E_2 \[PGE_2\], and VEGF). Tissue samples are also assessed by cDNA microarray and imaging mass spectrometry to determine overall changes in gene and protein expression from pretreatment levels. Surrogate markers of COX-2 activity in serum (i.e., VEGF) and urine (i.e., urinary metabolite of PGE_2 \[PGE-M\]) are also assessed and compared with changes noted in tumor tissue. COX-2 protein levels are determined by immunohistochemistry in patients with limited pretreatment tumor tissue specimens.

Study Timeline

• Study Start: 2002-07
• Primary Completion: 2004-05
• Study First Submitted: 2008-01-30
• Study First Submitted QC: 2008-02-02
• Study First Posted: 2008-02-06
• Study Completion: 2008-04
• Status Verified: 2013-03
• Last Update Submitted: 2013-03-02
• Last Update Posted: 2013-03-05

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Clinical diagnosis of primary adenocarcinoma of the rectum (to be histologically confirmed upon study entry)

  • Tumor must be at or below the peritoneal reflection
  • The distal border of the tumor is within 12 cm of the anal verge on proctoscopic examination

• Clinically resectable disease

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• WBC ≥ 4,000/mm³
• Platelet count ≥ 150,000/mm³
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other serious medical illness (other than rectal cancer) that would preclude study therapy
• No psychiatric condition that would preclude informed consent
• No history of allergy to celecoxib or any other NSAIDs, including acetylsalicylic acid (i.e., aspirin), ibuprofen, or indomethacin
• No history of allergy to sulfonamides

Exclusion criteria:

Not noted

PRIOR CONCURRENT THERAPY:

• At least 7 days since prior and no concurrent NSAIDs or other cyclooxygenase-2 inhibitors
• No concurrent warfarin, except low-dose warfarin (i.e., 1 mg/day) administered for prophylaxis

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Therapeutic Intervention/Celecoxib	therapeutic conventional surgery	Celecoxib
Therapeutic Intervention/Celecoxib	biopsy	Celecoxib
Therapeutic Intervention/Celecoxib	neoadjuvant therapy	Celecoxib
Therapeutic Intervention/Celecoxib	mass spectrometry	Celecoxib
Therapeutic Intervention/Celecoxib	celecoxib	Celecoxib
Therapeutic Intervention/Celecoxib	gene expression analysis	Celecoxib
Therapeutic Intervention/Celecoxib	protein expression analysis	Celecoxib
Therapeutic Intervention/Celecoxib	immunohistochemistry staining method	Celecoxib
Therapeutic Intervention/Celecoxib	laboratory biomarker analysis	Celecoxib

Primary Outcome Measures

Name	Time	Method
Event rate of over-expression of cyclooxygenase-2	Pre and post 7 days administration of study drug
Percent change of eicosanoid level	Pre and post celecoxib treatment ratio of eicosanoid production
Percent change of VEGF and prostaglandin-M levels	Pre and post celecoxib treatment VEGF and PGE-M levels
Change of gene and protein expression pattern from pre- to post-treatment levels	Pre and post celecoxib treatment

Trial Locations

Locations (2)

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Veterans Administration; 🇺🇸 Nashville, Tennessee, United States